Methods for the chromatographic separation of components of a multicomponent fluid mix according to the current state of the art are used in particular in the pharmaceutical and chemical industries for separating components of a mixture of substances having a high degree of purity even if this mixture of substances is a complex multicomponent fluid mix, the components of which might additionally be temperature-sensitive. Here, the different affinities of the components to be separated compared to a solid substance (preferably adsorbent material) are used for the separation thereof.
Conventionally, chromatographic separations are carried out discontinuously in a so-called batch process. In such a batch process, a solvent (eluant) is passed through a chamber (separation column) filled with the solid material. A limited amount of the sample to be separated is injected into a solvent stream. Due to the differences in the strength of the interactions, the components move through the separation column at different velocities and exit these at different times. This injection cannot be repeated until after a certain period of time, without affecting the separation success of the previous injection.
For a continuous operating mode, a counterflow between the liquid phase containing solvent and the solid phase is generated. To this end, the solid phase is moved in the opposite direction to the liquid phase.
In such an operating mode in a counterflow process, the multicomponent fluid mix may be applied continuously at the centre of the separation column. In the case of suitably selected flow ratios between the liquid and the solid phases, the component moving together with the solid substance and showing the stronger interaction may be fed in the direction of an extract stream carried out of the separation column and the component moving together with the liquid phase and showing the weaker interaction may flow in the direction of a raffinate stream also carried out.
The separation methods may be carried out in a continuous operating mode according to the known Simulated Moving Bed (SMB) method. Such methods are applied to apparatus which as a rule consist of at least four separation zones forming a loop, which consist of at least one chamber or chamber section. The actual counterflow of the solid phase is simulated by periodically moving the solid substance statically placed in individual chambers in the direction opposite to the flow of the solvent. This corresponds to the Moving Column principle. Alternatively, in the case of fixed chambers, also the positions of the inflow and outflow ports may be cyclically displaced. This corresponds to the Moving Port principle. The time between two switch-over processes is identified as the clock time. The zones are delimited by two inflows, one each for the multicomponent fluid mix and for the solvent, as well as by two outflows, one each for the extract and the raffinate stream. The separation of the components is for the most part carried out in two of the four zones, whereas the two further zones are used for the regeneration of the solid and liquid phases.
In such an SMB method, a self-repeating regime will develop after a certain period of time. This will be referred to as a cyclic steady state. In this state, characteristic concentration profiles, which repeat themselves after one clock period and which are caused by the periodic changeover, are present in the outlet streams.
U.S. Pat. No. 2,985,589 describes such an SMB method for the continuous chromatographic separation of multicomponent fluid mixes having a fixed adsorbent bed containing the solid substance as well repositionable inflows and outflows.
The method described in U.S. Pat. No. 2,985,589 is carried out at constant operation parameters such as the volume streams fed in and out, the time duration of a clock unit and the concentrations of the multicomponent fluid mix and the solvent fed in. It will be referred to below as the “conventional method”.
U.S. Pat. No. 5,102,553 describes an SMB method wherein the volume streams of the multicomponent fluid mix, the solvent, the extract stream, the raffinate stream and the in-circuit circulation streams, which are fed in and out, are designed to be time-variable within one clock unit (the “powerfeed” method). By this means, productivity may be enhanced compared to the SMB method at constant operation parameters.
In WO A 0025885 a process is suggested which provides for an asynchronous switching over of inflows and outflows. This corresponds to the VariCol method. Contrary to the conventional SMB method, the port positions of the inflows and outflows are newly positioned here at different points in time, so that variable separation zone lengths per unit time are obtained. In this way, an increase of productivity is achieved.
US 2006/023459 shows a variation of the VariCol method, wherein the concentration of the stream between two zones is increased by means of an additional process step.
WO 2004014511 describes an SMB method wherein the concentration of the multicomponent fluid mix fed in is changed within one clock unit. This corresponds to the ModiCon method.
By means of this method, an increase of productivity and of the product concentration as well as a reduction of the specific solvent use may be achieved by feeding in a higher concentrated multicomponent fluid mix for example in the fourth quarter of a clock period.
U.S. Pat. No. 2,985,589, U.S. Pat. No. 5,102,553 and WO 2004014511 describe methods which are based on a continuous collection of the effluent extract and raffinate streams. These methods have to be implemented in such a way that a specified high integral purity averaged across the entire clock period may be achieved. In the case of very high target purities, this is achieved at the cost of a lower productivity.
As an alternative, an SMB method is suggested in Y.-S. Bae and C.-H Lee “Partial discard strategy for obtaining high purity products using movid bed chromatography”, Journal of Chromatography A, 1122: 161-173 (2006), wherein only part of the effluent extract or raffinate stream is collected within one clock period (fractionation method). In the method described, the part not collected is discarded. A recirculation of the non-collected proportion into the receiver tank of the initial multicomponent fluid mix is suggested only for the case in which this tank is large and the proportion to be recirculated is small, in order to make sure that the inflow concentration of the multicomponent mix will not be changed. The method described in the Journal of Chromatography A, 1122: 161-173 (2206) has the disadvantage that a partial discarding of the outflow stream will cause reductions in productivity and yield.